1. Product Overview
dTRIM24 (CAS No. 2170695-14-2) is a potent, selective PROTAC (Proteolysis Targeting Chimera) that induces the cereblon (CRBN)-recruited ubiquitin-mediated degradation of Tripartite Motif Containing 24 (TRIM24), also known as Transcriptional Intermediary Factor 1 alpha (TIF1α). With molecular formula C55H68N8O13S2 and MW 1113.31 g/mol, it conjugates an ineffective TRIM24 bromodomain ligand to a thalidomide-derived CRBN E3 ligase recruiter via a triethylene-glycol-based flexible linker. dTRIM24 achieves near-complete TRIM24 depletion with DC50 in the low-nanomolar range (∼10–30 nM) in MOLM-13 and MV-4-11 acute myeloid leukemia (AML) cells, outperforming the parent bromodomain inhibitor (IACS-9571) in suppressing proliferation and inducing apoptosis (enhanced PARP cleavage). Originally reported by Gechijian et al. (Nat Chem Biol 2018), it is the canonical tool for dissecting TRIM24’s role as an epigenetic reader in AML, breast cancer, and liver tumorigenesis, and for comparing degradation vs inhibition in bromodomain-targeted epigenetics.
2. Key Features and Advantages
• Selective TRIM24 Degradation: DC50 ∼10–30 nM in AML lines; >100-fold selectivity over related bromodomains (BRD2/3/4, BRD7/8/9) and other epigenetic readers; recruits CRBN to form productive ternary complex.
• Degrader Superior to Inhibitor: Near-complete TRIM24 clearance within 4–6 h vs partial blockade by competitive bromodomain inhibitor; drives stronger anti-proliferative effects and sustained apoptotic priming in MOLM-13/ MV-4-11.
• Large PROTAC Scaffold: MW 1113.31, PEG3-linker connects TRIM24 BD ligand (benzoimidazole core with propoxyphenoxy) to thalidomide warhead; optimized for cellular permeability despite size.
• Validated In Vivo Relevance: Oral or IP dosing (30–100 mg/kg) achieves TRIM24 degradation in AML PDX and liver cancer models; suppresses oncogenic transcription (MYC, CCND1) linked to TRIM24 chromatin reading.
• Research-Grade Quality: ≥98% purity (HPLC), white to off-white solid; soluble in DMSO (>60 mg/mL max conc, sonication + 60 °C warming recommended); stable at -20°C for 2–3 years.
3. Main Applications
• Epigenetics & Bromodomain Research: Studying TRIM24 as a non-BET bromodomain reader regulating H3K23ac/H3K4me0 recognition, enhancer–promoter looping, and MYC transcription in AML and solid tumors.
• Acute Myeloid Leukemia Models: MOLM-13, MV-4-11, and primary AML blasts with high TRIM24 dependency; evaluating dTRIM24 vs IACS-9571 (inhibitor) or BRD4 PROTACs (ARV-771/ARV-825) in AML pharmacodynamics.
• PROTAC Technology Development: Reference TRIM24 degrader for linker-length SAR, ternary complex crystallography, and designing dual degraders (e.g., TRIM24–BRD4 co-degrader); comparator to dBRD9 (BRD9 PROTAC).
• Degradation vs Inhibition Studies: Directly comparing protein removal (dTRIM24) with occupancy-based blockade (IACS-9571/VL-269/eTRIM24) to quantify functional consequences on chromatin state and cell fate.
• Liver Cancer & Breast Cancer Research: TRIM24 is amplified/overexpressed in hepatocellular carcinoma and ER+ breast cancer; dTRIM24 probes dependency and combination with KRAS/MAPK or CDK4/6 inhibitors.
4. Technical Specifications
5. Storage and Handling
Store powder at -20°C in a tightly sealed, desiccated container protected from light; stable for 2–3 years. Prepare DMSO stock at 5–10 mg/mL with sonication and gentle warming to 60 °C (large PROTAC with PEG-linker dissolves slowly at RT); aliquot to avoid freeze-thaw and store at -80°C up to 6 months or -20°C up to 1 month. For in vivo, formulate in 10% DMSO with 90% saline or corn oil/Tween80 at 1–5 mg/mL; sonicate to clarity. Allow vial to reach room temperature before opening; weigh in fume hood with nitrile gloves and goggles. Contains thalidomide-type warhead—handle as potent bioactive/epigenetic degrader with teratogenic potential; avoid dust inhalation and skin contact.
6. Safety Overview
For laboratory research use only, not for human/veterinary therapeutic or diagnostic use. GHS07 possible (H302 harmful if swallowed, H315/H319 skin/eye irritant). Handle as bioactive PROTAC with epigenetic and teratogenic thalidomide motif; wear nitrile gloves, goggles, lab coat; use in fume hood when weighing. Dispose as hazardous organic chemical waste per local regulations. Include DMSO/saline vehicle controls in all cell (AML PDX, MOLM-13) and animal assays.
